Fatty acids in excess impair mechanical function and electrical stability in ischemic hearts. The purpose of the present studies was to test whether
oxfenicine, an agent capable of reducing
fatty acid metabolism, can prevent these consequences and in so doing improve hemodynamic performance. Two groups of working swine hearts (n = 15), extracorporeally perfused with whole blood, were compared over 90 min of controlled coronary perfusion. An
emulsion of
triacylglycerols (
Intralipid) with
heparin were administered systemically to augment serum
fatty acids threefold (0.30 to 0.92 mumol/ml). Labeled [U14C]
palmitate was administered selectively into the left anterior descending coronary circulation to follow
fatty acid oxidation. Coronary flow in this bed was decreased by 50% over the final 30 min of perfusion. Saline (n = 7) or
oxfenicine (17-33 mg/kg, n = 8) was administered to placebo or treated animals at 30 min perfusion. 14CO2 production from labeled
palmitate was decreased by 55% (P less than 0.025) at normal flows in
oxfenicine-treated hearts and was reduced further during
ischemia. Tissue levels of acyl
carnitine were significantly reduced and
acetyl CoA levels significantly increased in
oxfenicine-treated hearts both in aerobic and ischemic myocardium. These changes were associated with an improvement in mechanical function. Left ventricular systolic and developed pressures and maximum left ventricular dP/dt were increased by 36 delta %, P less than 0.01; 46 delta %, P less than 0.025; and 41 delta %, P less than 0.025, respectively, at end
ischemia as compared with placebo hearts.(ABSTRACT TRUNCATED AT 250 WORDS)